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Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (LINK)

Primary Purpose

Colon Cancer Liver Metastasis

Status

Unknown status

Phase

Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

NKR-2 cells

About this trial

This is an interventional treatment trial for Colon Cancer Liver Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

The patient must be ≥ 18 years old at the time of signing the ICF.
The patient must have a histologically proven adenocarcinoma of the colon or rectum.
The patient must have liver metastases non treatable with curative intent by surgical resection or local ablation at the time of registration.
The patient must have measurable hepatic metastases defined by RECIST version 1.1 for solid tumors.
The patient must have received one prior chemotherapy line for metastatic disease and have developed resistance or intolerance to this treatment.
The patient must have an ECOG performance status 0 or 1.
The patient must have the bone marrow reserve, hepatic and renal functions

Exclusion Criteria:

Patients who are presenting evidence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
Patients who are planned to receive or concurrently receiving any non-cancer-directed investigational agent, or have received a non-cancer directed investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
Patients who are scheduled to receive concurrent growth factor (except erythropoietin), systemic steroid, other immunosuppressive therapy or cytotoxic agents (systemic or localized) other than the treatment authorized per protocol.
Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration.
Patients who have received a live vaccine ≤ 6 weeks prior to the planned day for the first NKR-2 administration.
Patients with a family history of congenital or hereditary immunodeficiency.
Patients with history of any autoimmune disease.

Sites / Locations

Institut Jules Bordet

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose-level 1

Dose-level 2

Dose-level 3

Arm Description

The dose-level 1 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

The dose-level 2 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

The dose-level 3 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

Outcomes

Primary Outcome Measures

The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43)

A DLT is defined as any Grade 3 or higher toxicity and any Grade 2 or higher autoimmune toxicity

Secondary Outcome Measures

The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)

AEs and SAEs collection

The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))

Complete response (CR), partial response (PR)

The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD))

Complete response (CR), partial response (PR) and stable disease (SD)

The occurrence and duration of mixed response (MR)

The different types of MR are defined according to the following criteria: at least 30% decrease in the longest diameter (or shortest diameter for nodal lesions) occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise SD or PD status of the sum of diameters of target lesions and without the appearance of one or more new lesions will be classified as "MR (SD)", which corresponds to a SD with target lesion regression or "MR (PD)", which corresponds to PD with target lesion regression and, the appearance of new lesion(s) in otherwise PR status of the sum of diameters of target lesions will be classified as "MR (PR)", which corresponds to a PR with new lesion.

The resection rate at Visits Day 57 and Month 3

Assessment of R0, R1 and R2 resections

The progression-free survival (PFS)

The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause

The event-free survival (EFS)

The event-free survival (EFS) is defined as the time from registration in the study to any of the following events: progression, local or distant recurrence, or death from any cause

The overall survival (OS).

The overall survival (OS) is defined as the time from registration in the study to death. If death does not occur before the patient's last study visit, then the survival will be censored at the date when patient is known to be alive

Full Information

NCT ID

NCT03370198

First Posted

November 8, 2017

Last Updated

June 18, 2020

Sponsor

Celyad Oncology SA

1. Study Identification

Unique Protocol Identification Number

NCT03370198

Brief Title

Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

Acronym

LINK

Official Title

An Open-label Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Unknown status

Study Start Date

October 11, 2017 (Actual)

Primary Completion Date

January 15, 2019 (Actual)

Study Completion Date

December 15, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celyad Oncology SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to test an experimental anti-cancer immunotherapy called NKR-2 (modified T cells), to treat colorectal cancer with unresectable liver metastases. The trial will test three dose levels (dose escalation). At each dose, the patients will receive three successive hepatic transarterial administrations, two weeks apart, of NKR-2 cells. The study will enroll up to 18 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer Liver Metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

There will be a hepatic transarterial administration of NKR-2 every 2 weeks for a total of 3 administrations within 4 weeks (28 days). Three dose-level will be assessed (dose escalation with 3 dose-levels or 3 cohorts).

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose-level 1

Arm Type

Experimental

Arm Description

The dose-level 1 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

Arm Title

Dose-level 2

Arm Type

Experimental

Arm Description

The dose-level 2 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

Arm Title

Dose-level 3

Arm Type

Experimental

Arm Description

The dose-level 3 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)

Intervention Type

Biological

Intervention Name(s)

NKR-2 cells

Other Intervention Name(s)

NKG2D CAR-T cells

Intervention Description

NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days)

Primary Outcome Measure Information:

Title

The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43)

Description

A DLT is defined as any Grade 3 or higher toxicity and any Grade 2 or higher autoimmune toxicity

Time Frame

From study treatment start (Day 1) till 14 days after the last NKR-2 study treatment administration (Day 43)

Secondary Outcome Measure Information:

Title

The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)

Description

AEs and SAEs collection

Time Frame

From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57)

Title

The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))

Description

Complete response (CR), partial response (PR)

Time Frame

through study completion (up to month 24)

Title

The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD))

Description

Complete response (CR), partial response (PR) and stable disease (SD)

Time Frame

through study completion (up to month 24)

Title

The occurrence and duration of mixed response (MR)

Description

Time Frame

through study completion (up to month 24)

Title

The resection rate at Visits Day 57 and Month 3

Description

Assessment of R0, R1 and R2 resections

Time Frame

At visits Day 57 and Month 3

Title

The progression-free survival (PFS)

Description

The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause

Time Frame

through study completion (up to month 24)

Title

The event-free survival (EFS)

Description

The event-free survival (EFS) is defined as the time from registration in the study to any of the following events: progression, local or distant recurrence, or death from any cause

Time Frame

through study completion (up to month 24)

Title

The overall survival (OS).

Description

Time Frame

through study completion (up to month 24)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: The patient must be ≥ 18 years old at the time of signing the ICF. The patient must have a histologically proven adenocarcinoma of the colon or rectum. The patient must have liver metastases non treatable with curative intent by surgical resection or local ablation at the time of registration. The patient must have measurable hepatic metastases defined by RECIST version 1.1 for solid tumors. The patient must have received one prior chemotherapy line for metastatic disease and have developed resistance or intolerance to this treatment. The patient must have an ECOG performance status 0 or 1. The patient must have the bone marrow reserve, hepatic and renal functions Exclusion Criteria: Patients who are presenting evidence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis as determined by clinical or radiologic assessment. Patients who are planned to receive or concurrently receiving any non-cancer-directed investigational agent, or have received a non-cancer directed investigational agent within 3 weeks before the planned day for the first NKR-2 administration. Patients who are scheduled to receive concurrent growth factor (except erythropoietin), systemic steroid, other immunosuppressive therapy or cytotoxic agents (systemic or localized) other than the treatment authorized per protocol. Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration. Patients who have received a live vaccine ≤ 6 weeks prior to the planned day for the first NKR-2 administration. Patients with a family history of congenital or hereditary immunodeficiency. Patients with history of any autoimmune disease.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frédéric Lehmann, MD

Organizational Affiliation

Celyad Oncology SA

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut Jules Bordet

City

Brussels

ZIP/Postal Code

1000

Country

Belgium

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

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